Bioactive Polyhydroxanthones from Penicillium purpurogenum.

ABSTRACT

Eight new polyhydroxanthones, penicixanthones A-H (1-8), including four monomers (1-4) and four dimers (5-8), were isolated from solid cultures of Penicillium purpurogenum SC0070. Their structures were elucidated by extensive spectroscopic analysis, X-ray single-crystal diffraction, and theoretical computations of ECD spectra. Penicixanthone B (2) has a hexahydroxanthone structure featuring an unusual oxygen bridge between C-6 and C-8a. Penicixanthone D (4) is distinct from other penicixanthones in stereochemistry, and its biosynthetic mechanism was proposed based on theoretical simulations for the reaction pathway of C-10a epimerization. Penicixanthone G (6) exhibited the most potent cytotoxicity (IC50 0.3-0.6 µM) when tested against human carcinoma A549, HeLa, and HepG2 cells, whereas it was nontoxic to the normal Vero cells (IC50 > 50 µM). It also displayed the strongest antibacterial activity (MIC 0.4 µg/mL) against both Staphylococcus aureus and the methicillin-resistant strain MRSA.